title: Cross-reactivity patterns of contact-sensitizing methacrylates.
abstract: Methacrylates are well-known contact sensitizers with increasing frequency of contact leading to occupational skin disease. Here, we developed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 microliters of 1.0 M methacrylate solutions in Freund's complete adjuvant into both flanks, both ears, and the neck. After 14 days open skin tests were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA solutions in 40% DMSO in ethanol. Cross-reactivities were investigated 14 days later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates could be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-HPMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequent cross-reactivities, 2-HEMA sensitization led to strong cross-reactions to all other methacrylates. Both MMA and 2-HPMA induced strong cross-reactivity to EGDMA but only weak to moderate reactivities to the other methacrylates. The absence of strong cross-reactions with monomethacrylates in EGDMA (dimethacrylate)-sensitized animals may be explained by the predominance of highly EGDMA-specific T-cells in these animals. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylates, according to their molecular similarities. The strong skin hypersensitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hypersensitivities and common cross-sensitization patterns in clinical practice.
authors.affiliation: Department of Pathology, Free University Hospital of Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Rustemeyer
authors.forename: J
authors.initials: J
authors.lastname: de Groot
authors.forename: B M
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Frosch
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D012867:Skin / Q000276:immunology; D012882:Skin Tests / Q000379:methods; D013329:Structure-Activity Relationship
chemical_list: D000485:Allergens; D008689:Methacrylates